Immune responses to Plasmodium vivax pre‐erythrocytic stage antigens in naturally exposed Duffy‐negative humans: a potential model for identification of liver‐stage antigens

• Published in: European journal of immunology Vol. 35; no. 6; pp. 1859 - 1868
• Main Authors: Wang, Ruobing, Arevalo‐Herrera, Myriam, Gardner, Malcolm J., Bonelo, Anilza, Carlton, Jane M., Gomez, Andres, Vera, Omaira, Soto, Liliana, Vergara, Juana, Bidwell, Shelby L., Domingo, Alexander, Fraser, Claire M., Herrera, Socrates
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01-06-2005
• Subjects: Acquired immunity; Adult; Animals; Antigens, Protozoan - immunology; Cross Reactions; Duffy antigen; Duffy Blood-Group System - analysis; Erythrocytes - parasitology; Female; Genome, Protozoan; Humans; IFN‐γ; Interferon-gamma - biosynthesis; Liver - parasitology; Male; Middle Aged; Plasmodium vivax; Plasmodium vivax - genetics; Plasmodium vivax - immunology; Pre‐erythrocytic stage
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200425807

Duffy antigen is the receptor used by Plasmodium vivax to invade erythrocytes. Consequently, individuals lacking Duffy antigen [Fy(–)] do not develop blood‐stage infections. We hypothesized that naturally exposed Fy(–) humans may develop immune responses mainly to pre‐erythrocytic stages and could be used to study acquired immunity to P. vivax and to identify liver‐stage antigens. We report here that antibody and IFN‐γ responses to known sporozoite antigens were significantly induced by natural exposure in Fy(–) humans, whereas responses to blood‐stage antigens were significantly induced in Fy(+) humans. IFN‐γ responses to sporozoite antigens were lower in Fy(+) than in Fy(–) humans, indicating that in Fy(+) humans blood‐stage infections may have suppressed T cell responses to pre‐erythrocytic stages. We evaluated the immune responses to 18 novel P. vivax homologs of P. falciparum sporozoite proteins identified from the P. vivax genome sequence. Eight proteins recalled IFN‐γ responses in P. vivax‐exposed but not in unexposed individuals. Of these, 3 antigens elicited IFN‐γ responses in Fy(–) but not in Fy(+) individuals. These results suggest that differential immune responses observed in naturally exposed Fy(–) and Fy(+) individuals can be exploited to identify P. vivax stage‐specific antigens.